Potential applications of surface-immobilized antimicrobial polymers include, for example, as coatings on medical devices, water purification systems, food packaging, and hospital equipment. Bacterial infections on implanted medical devices such as catheters and pacemakers can lead to serious complications and often, to device removal, because the adherent bacterial can form a biofilm, which provides a protective environment for bacteria, allowing them to resist killing by antibiotics, as well as immune responses.
Strategies to limit bacterial fouling of surfaces can incorporate either passive or active elements. Passive approaches to fouling prevention lack an active antibacterial component and typically involve the use of antifouling polymer surface coatings to provide steric resistance to physical attachment of bacteria. Examples of polymers and/or polymeric components that have been shown to reduce short-term bacterial attachment include poly(ethylene glycol) (PEG), self-assembled monolayers (SAMs), and peptidomimetic polymers.
Surface coatings may also contain active components capable of killing bacteria through direct contact or via a leachable compound. Examples of active antibacterial coatings include cationic polymers such as chitosan and polymers containing quaternary ammonium and pyridinium functional groups. The antibacterial effect of silver can be exploited by incorporation of silver salts or silver nanoparticles into coatings. Another reported approach for creating antibacterial surfaces involves the direct attachment of antibiotics such as vancomycin and penicillin to surfaces. Alternatively, antimicrobial peptides (AMPs) offer activity against a wide range of organisms, while functioning with some selectivity for bacteria over mammalian cells, and there have been recent reports of AMP imobilization on surfaces.
Several non-natural mimics of antimicrobial peptides with high activity have recently been developed, providing advantages in terms of chemical diversity and significant resistance to protease degradation. For example, the linear cationic α-helical class of AMPs has been successfully mimicked as β-peptides and as poly-N-substituted glycines (peptoids). Peptoids are non-natural mimics of polypeptides with their side chains appended to the amide nitrogen instead of to the α-carbon. Peptoids are well suited for antibacterial peptide use because they have been shown to be resistant to proteolytic enzymes; the well-known submonomer synthesis method of Zuckermann et al. allows for great versatility of the side-chain chemistry; and conformationally stable helical secondary structures can be formed by incorporating sterically bulky, α-chiral side chains. Peptoid mimics of antimicrobial peptides (ampetoids) with helical structures that exhibit antibacterial activity in solution have been synthesized previously. (See, Patch J A, Barron A E (2003) Helical Peptoid Mimics of Magainin-2 Amide. Journal of the American Chemical Society, 125, 12092-12093; and Chongsiriwatana N P, Patch J A, Czyzewsli A M, Dohm M T, Ivankin A, Gidalevitz D, Zuckermann R N, Barron A E (2008) Peptoids that mimic the structure, function, and mechanism of helical antimicrobial peptides. Proceedings of the National Academy of Science USA, 105, 2794-2799, each of which is incorporated herein by reference in its entirety.) Several ampetoids were recently tested for broad-spectrum activity against bacteria, as wel as for cytotoxicity against various mammalian cells, revealing certain sequence-specific oligopeptoids that have antibacterial activities equivalent to or better than cationic antimicrobial peptides and with strong selectivity for killing bacteria over mammalian cells; and co-pending application Ser. No. 12/378,034 filed Feb. 9, 2009, also incorporated herein by reference in its entirety.
Certain peptoids, with different sequences and chain lengths, can also offer passive resistance to biofouling much like other antifouling polymers, as was first established with surfaces coated with a linear poly(N-methoxyethyl glycine), or pNMEG peptoid. (See, co-pending application Ser. No. 11/280,107, filed Nov. 16, 2005, the entirety of which is incorporated herein by reference.) Protein and cell adhesion onto TiO2 was dramatically reduced by coating with this peptoid, which has side-chains similar to the repeat unit of polyethylene glycol (PEG). A follow-up study revealed a dramatic reduction in Staphylococcus epidermidis and Escherichia coli bacterial adhesion when compared to unmodified TiO2 substrates, presumably due to the pNMEG peptoid's passive inhibition of bacterial cell attachment by virtue of its unique chemical structure.